Dysphagia, Spatial Neglect
Conditions
Keywords
Spatial Neglect, Dysphagia, Arousal, Modafinil, Stroke
Brief summary
The purpose of this study is to examine how stroke can alter arousal, alertness, neglect and dysphagia, and whether a medication, modafinil, can improve arousal.
Detailed description
Neglect and dysphagia are two of the most problematic behavioral disorders encountered in stroke rehabilitation with 300,000 patients affected annually in the US. Both disorders impede progress in therapy and both lead to costly medical complications, like falls which are associated with neglect and aspiration pneumonia and malnutrition which are associated with dysphagia. No widely accepted pharmacological treatment exists for either disorder. A new direction of this application is to view neglect and dysphagia as different disorders that share a common deficit in magnitude estimation (ME). ME refers to one's ability to perceive the intensity of sensory stimulation. Deficits in ME explain how much of a stimulus is neglected by stroke patients. Sensory deficits are also known to produce dysphagia. Perceptual deficits influence how patients response to stimuli like failing to act on all stimuli present (neglect) and failing to generate swallowing reflexes sufficient for normal bolus flow (dysphagia). We know from previous work that ME is altered by change in cortical arousal following stroke (decreased or hypoarousal). Hypoarousal is evidenced by objective and subjective post-stroke fatigue and daytime sleepiness which occurs in 50% of stroke patients and can persist chronically. Increasing arousal could potentially reverse the perceptual deficits associated with hypoarousal and improve neglect and dysphagia. This proposal manipulates arousal in two ways. Cold pressor stimulation (CPS), immersing the foot in cold water for 50 seconds, is used to increase arousal and reverse neglect and dysphagia temporarily. A brief, 3-day trial of modafinil (Provigil) versus placebo is then used in stroke patients to learn if a positive response to cold-pressor stimulation can predicts patients who respond positively to modafinil.
Interventions
DRUGModafinil
200 mg once daily with morning meal for three days administered only to stroke patients
DRUGPlacebo
Subjects will receive a placebo designed to look like 200 mg dose of modafinil. The dose will be taken once daily with the morning meal for three days and will only be administered to stroke patients
BEHAVIORALBaseline
Observations made at baseline before any intervention
BEHAVIORALCPS
Submerging each participant's foot into ice water (36-44 F) for 50 seconds.
BEHAVIORALPost CPS
20 minutes following the CPS condition.
BEHAVIORALFollow up
Follow up testing occurred at 3 months
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
University of Arkansas
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Willingness to complete study procedures * Ability to comprehend and sign informed consent * Evidence of unilateral, ischemic stroke based on: * Neuroimaging (clinically obtained imaging studies showing evidence of stroke) * Acceptable categories of stroke include: * Unilateral ischemic stroke * Atherothrombotic stroke * Cardioembolic stroke * Lacunar stroke \>1.5 cm * Chronic stable, unilateral hemorrhagic stroke * Or Behavioral evidence of stroke including: * Hemiplegia * Unilateral sensory impairment * Localized higher cortical dysfunction (e.g. neglect,dysphagia, apraxia)
Exclusion criteria
* Cardiac valvular disease * Left heart hypertrophy * Poorly controlled hypertension * Active variant angina * Pre-menopausal women capable of having children, including those using active contraception (precaution for study medication and not applicable to normal subjects) * Severe renal or hepatic disease * History of psychosis or substance abuse * Patients on other Central Nervous System (CNS) stimulants, dopamine agonists or antagonists (antipsychotics) * Severe speech comprehension deficit and/or inability to communicate responses * Allergies that could put the research subject at risk during the course of the study * Cannot speak English * Active cerebral neurologic disease other than stroke such as multiple sclerosis or Alzheimer's Disease * Active psychiatric illness except past history of treated depression or anxiety disorders * For persons needing an MRI - standard MRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| P50 Percent Habituation Score | baseline and after three days of intervention | This is an electrophysiological measure of arousal - a percent change in the P50 evoked response potential amplitudes with a 250 ms inter stimulus interval. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PVT Fastest 10 Percent of Reaction Times | baseline and after three days of intervention | This is a behavioral measure of arousal - the fastest 10 percent of all cued reaction time trials. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only). |
| Power Function Exponent for Oral Bolus Estimation | baseline and after three days of intervention | This is a behavioral measure of sensation in the oral cavity. The power function exponent is equal to the slope of a regression equation relating bolus size to a person's estimate of that size. An exponent below one implies an underestimate of bolus size. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only). |
| Time to Swallow Puree Food | baseline and after three days of intervention | This is a behavioral measure of swallowing - the time it takes for pureed food to transition across a part of the throat. The difference score is calculated as CPS - placebo and as modafinil - placebo (for stroke subjects only). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normal Subjects Normal subjects are persons without stroke who receive baseline, CPS, Post CPS and Follow up interventions.
Baseline: Observations made at baseline before any intervention
CPS: Submerging each participant's foot into ice water (36-44 F) for 50 seconds.
Post CPS: 20 minutes following the CPS condition. | 21 |
| Stroke Subjects Stroke subjects are persons who have had a stroke affecting the right hemisphere and are subject to neglect or dysphagia who receive baseline, CPS, and Post CPS and then are randomized to modafinil or placebo.
Baseline: Observations made at baseline before any intervention
CPS: Submerging each participant's foot into ice water (36-44 F) for 50 seconds.
Post CPS: 20 minutes following the CPS condition. Modafinil: 200 mg once daily with morning meal for three days administered only to stroke patients
Placebo: Subjects will receive a placebo designed to look like 200 mg dose of modafinil. The dose will be taken once daily with the morning meal for three days and will only be administered to stroke patients | 7 |
| Total | 28 |
Baseline characteristics
| Characteristic | Stroke Subjects | Total | Normal Subjects |
|---|---|---|---|
| Age, Continuous | 71.429 years STANDARD_DEVIATION 9.914 | 58.2 years STANDARD_DEVIATION 15.3 | 51.286 years STANDARD_DEVIATION 21.462 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 6 Participants | 24 Participants | 18 Participants |
| Sex: Female, Male Female | 3 Participants | 11 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 17 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 21 | 6 / 7 |
| serious Total, serious adverse events | 0 / 21 | 2 / 7 |
Outcome results
Primary
P50 Percent Habituation Score
This is an electrophysiological measure of arousal - a percent change in the P50 evoked response potential amplitudes with a 250 ms inter stimulus interval. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only).
Time frame: baseline and after three days of intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Subjects: Baseline vs CPS | P50 Percent Habituation Score | -44.12 percentage of change in amplitude | Standard Deviation 59.29 |
| Stroke Subjects: Baseline vs CPS | P50 Percent Habituation Score | -45.84 percentage of change in amplitude | Standard Deviation 228.09 |
| Stroke Subjects: Modafinil | P50 Percent Habituation Score | 113.63 percentage of change in amplitude | Standard Deviation 154.5 |
| Stroke Subjects: Placebo | P50 Percent Habituation Score | 61.41 percentage of change in amplitude | Standard Deviation 102.5 |
| Stroke Subjects Placebo vs Modafinil | P50 Percent Habituation Score | 52.223 percentage of change in amplitude | Standard Deviation 222.94 |
Secondary
Power Function Exponent for Oral Bolus Estimation
This is a behavioral measure of sensation in the oral cavity. The power function exponent is equal to the slope of a regression equation relating bolus size to a person's estimate of that size. An exponent below one implies an underestimate of bolus size. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only).
Time frame: baseline and after three days of intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Subjects: Baseline vs CPS | Power Function Exponent for Oral Bolus Estimation | .014 exponent | Standard Deviation 0.113 |
| Stroke Subjects: Baseline vs CPS | Power Function Exponent for Oral Bolus Estimation | -.004 exponent | Standard Deviation 0.196 |
| Stroke Subjects: Modafinil | Power Function Exponent for Oral Bolus Estimation | .54 exponent | Standard Deviation 0.17 |
| Stroke Subjects: Placebo | Power Function Exponent for Oral Bolus Estimation | .49 exponent | Standard Deviation 0.19 |
| Stroke Subjects Placebo vs Modafinil | Power Function Exponent for Oral Bolus Estimation | .04 exponent | Standard Deviation 0.08 |
Secondary
PVT Fastest 10 Percent of Reaction Times
This is a behavioral measure of arousal - the fastest 10 percent of all cued reaction time trials. The difference score is calculated as CPS - baseline and as modafinil - placebo (stroke subjects only).
Time frame: baseline and after three days of intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Subjects: Baseline vs CPS | PVT Fastest 10 Percent of Reaction Times | -10.57 milliseconds | Standard Deviation 21.66 |
| Stroke Subjects: Baseline vs CPS | PVT Fastest 10 Percent of Reaction Times | 20.57 milliseconds | Standard Deviation 29.2 |
| Stroke Subjects: Modafinil | PVT Fastest 10 Percent of Reaction Times | 244.71 milliseconds | Standard Deviation 186.62 |
| Stroke Subjects: Placebo | PVT Fastest 10 Percent of Reaction Times | 235.64 milliseconds | Standard Deviation 150.62 |
| Stroke Subjects Placebo vs Modafinil | PVT Fastest 10 Percent of Reaction Times | 9.07 milliseconds | Standard Deviation 38.73 |
Secondary
Time to Swallow Puree Food
This is a behavioral measure of swallowing - the time it takes for pureed food to transition across a part of the throat. The difference score is calculated as CPS - placebo and as modafinil - placebo (for stroke subjects only).
Time frame: baseline and after three days of intervention
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Subjects: Baseline vs CPS | Time to Swallow Puree Food | .029 seconds | Standard Deviation 0.121 |
| Stroke Subjects: Baseline vs CPS | Time to Swallow Puree Food | -.058 seconds | Standard Deviation 0.512 |
| Stroke Subjects: Modafinil | Time to Swallow Puree Food | .48 seconds | Standard Deviation 1.05 |
| Stroke Subjects: Placebo | Time to Swallow Puree Food | .12 seconds | Standard Deviation 0.11 |
| Stroke Subjects Placebo vs Modafinil | Time to Swallow Puree Food | .36 seconds | Standard Deviation 1.06 |